This proposal aims at the elucidation of those mechanisms underlying the initiation of the alternate pathway of complement activation; in so doing, the primary focus will be on a newly uncovered metabolic pathway, designated the Properdin Activator System. Primary objectives will be: 1) To ferret out the precise mechanisms by which properdin convertase, the enzyme responsible for properdin activation, is itself activated by complex polysaccharides. This involves further isolation and definition of an intermediate protein, C3NeF, which is required for properdin convertase activation 2) To define the exact way in which activated properdin convertase interacts with native properdin 3) To pinpoint the manner in which activated properdin interacts with C3 and/or C5 and ultimately with C3 proactivator through C3 proactivator convertase. More precisely, emphasis will be on the nature of the C3 and/or C5 alteration that leads to recruitment of C3 proactivator activiy and utilization of terminal complement activity. This will involve isolation and characterization of the C3 and/or C5 intermediate products generated by activated properdin as well as an analysis of the intimate relationship between properdin, C3 and C3PAase. 4) To determine the relationship of the fluid phase Properdin Activator System to those enzymatic systems utilizing C3 proactivator at the surface of a complex polysaccharide. Particular attention will be give to the role of bound preperdin, if any, in the biology of the alternate pathway. 5) To characterize the participation of the various preteins in the Properdin Activator System in certain complement dependent disorders. In general, methodology will include routine immunochemical determinations, the use of purified proteins and radioactive labelling techniques as well as basic preparative procedures.